Researchers examined the effectiveness and adverse effects linked with switching to bupropion sustained release, augmenting treatment with bupropion, or augmenting treatment with aripiprazole.

In the VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) randomized clinical trial, augmenting antidepressant treatment with aripiprazole led to a greater response than switching to or augmenting with bupropion in patients with treatment-resistant major depressive disorder.1

An estimated 16.1 million adults in the United States suffer from major depressive disorder, and less than one-third of patients adequately respond to their first course of antidepressant medication.2,3 Common alternate strategies for these patients include switching to the antidepressant bupropion and adjunctive use of either bupropion or the antipsychotic aripiprazole.4

Although preliminary findings support the effectiveness of switching to or augmenting with bupropion or aripiprazole, these and other agents have not been compared in adequately powered clinical trials.5,6 In the current study, researchers examined the effectiveness of and adverse effects associated with 3 strategies commonly used with patients who do not respond to an initial round of treatment: switching to bupropion sustained release, augmenting treatment with bupropion sustained release, or augmenting treatment with aripiprazole.

The sample included 1522 patients at 35 US Veterans Health Administration medical centers with a diagnosis of major depressive disorder and a suboptimal response to previous antidepressant treatment. Response was considered suboptimal if scores on the 16-Item Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C16) questionnaire indicated severe depression after 6 weeks of treatment, or moderately severe depression after 8 weeks of treatment.

There were no significant differences between treatments, in terms of relapse outcomes

The bupropion switch (24.3%) and augmentation (22.5%) groups experienced more frequent anxiety than the aripiprazole group (16.6%).

The aripiprazole group experienced more frequent adverse effects such as fatigue, weight gain, somnolence, and akathisia compared with the other groups.

Future research should analyze the benefits and risks of augmenting with aripiprazole, considering the modest reduction in depression observed in the current study together with the risk for adverse effects. "Although use of the augment-aripiprazole strategy as an alternative treatment may offer an increased likelihood of remission, patients should be alerted to the risk of weight gain in a process of shared decision making," and metabolic values should be regularly monitored, the authors wrote.